Abstract Periodontal and craniofacial surgeries frequently require bone regeneration when patients suffer from severely resorbed alveolar bone and poor maxillary floor, craniofacial trauma, or congenital cleft palate. Current treatments rely on osteoinductive autografts and allografts to induce clinically significant bone regeneration whereas osteoconductive bone substitutes cannot. However, autografts are limited by availability and second morbidity and allografts are limited by inferior and unpredictable healing outcomes. Osteogenic bone morphogenetic proteins (such as BMP-2) are potent bone inducer therefore they are very attractive for periodontal and craniofacial bone regeneration. However, traditionally BMPs are only effective at supraphysiological doses which can induce significant complications and high surgery cost. Reducing dose requirement is urgently needed for their safer and cost-effective clinical use. We hypothesize a new intrinsically osteoinductive biomaterial can reduce the dose requirement of BMP-2 while serve as an osteoconductive scaffold. We propose a compensating or synergistic effect may significantly promote bone formation because of the combination, and the BMP-2 dose requirement will decrease with the increase of the level of the intrinsic osteoinductive ability. Such a combined approach has not been reported yet. A novel micro-concave hydroxyapatite hemispheres (McHAs) will be developed for the study. To test our hypothesis, we propose to (1) Develop high-quality McHAs with controlled micro-concavity size and degradation rate that can induce varied osteoinductive-like ability; (2) In vitro examine the osteoinductive-like property of McHAs; (3) In vitro evaluate the effect of McHAs on dose requirement of BMP-2 (4) In vivo evaluate the effect of McHAs on dose requirement of BMP-2. The success of the project will generate a new type of clinically safer, cost-effective bone graft substitute that can greatly improve osseous regeneration in periodontal and craniofacial surgeries. In addition, the research activity will significantly enrich and strengthen the biomedical research initiatives at our institute, by prompting new research themes, promoting collaboration among departments, faculty and laboratories, and training students in our biomedical related programs.